The Amyotrophic Lateral sclerosis(ALS)Research center set up with NINCDS funding uses multidisciplinary approaches. Collection of large groups of classified and monitored patients are our basis for collaborative studies correlated with clinical state and for developing specific treatment when indicated by our or other research. Constructive relations with patients secures cooperation for clinical specimens and post-mortem materials for investigative programs. Ultrastructural analysis of affected and unaffected areas of CNS will define neuronal chromatolysis, spheroid formation and Bunina bodies. Neuron cultures will test for neutrocytoxic factors (NCTF) in CSF and eluates of CNS. NCTF will be isolated from ALS serum with biophysical and immunochemical techniques and defined biologically and biochemically. Infusion of NCTF by continuous intraventricular injection into hydrocephalic cats may reproduce the in vitro effect and provide an animal model of motor neuron disease and a means of testing agents in vivo as well as in vitro that directly counteract NCTF or its effect. Neurochemistry studies showing abnormal distribution of gangliosides in ALS frontal cortex will be extended to other areas and to establish if disturbance of ganglioside syunthesis exists in ALS CNS. Abnornal glycoproteins will be isolated from ALS CNS and used as determinants for immune reactions with ALS serum andlymphocytes. Immune complexes (IC) in ALS astrocytes and serum will be disassociated and studied for antibody specificity with viral and CNS antigens. Isolated serum IC will be tested for infectivity andused to immunize rabbits. Antibody produced to antigen moiety will be tested for viral and CNS antigen reactivity and neurocytotoxic activity. Virus activity at cellular and molecular levels will be analyzed with cultures of brain explants isolated neurons and astrocytes and heterkaryons produced with these. Unique polypeptides, possibly virus associated will be looked for in 2d PAGE of isolated cells. A murine model of motor neuron disease due to lactic dehy drogenase virus will show age related susceptibility to virus and autoimmune mechanisms with ELISSA and cell mediated tests. This model has immunological, viral, genetic parameters and similar multifactors may be opeative in ALS. All programs will extend our initial discoveries and give insight into effectively modifying ALS.